Enigma of IL-17 and Th17 Cells in Rheumatoid Arthritis and in Autoimmune Animal Models of Arthritis

Table 1

Summary of the most important data about IL-17 in animal models of RA.

Model	Experiment	Effect	Reference
SKG	IL-17^−/− mice	Inhibited arthritis	[38]
	IL-6^−/− mice	Inhibited arthritis	[38]
	IFN-γ^−/−	Exacerbated arthritis	[38]
	a-CD4	Prevented arthritis (altering /Th17 ratio)	[39]
	a-IL-17A	Inhibited arthritis progression	[40]
K/BxN	a-IL-17	Slower disease progression	[41]
	Neomycin	Exacerbated arthritis (Th17 differentiation)	[41]
K/BxN serum	IL-17A^−/− mice	Less severe disease	[42]
	IL-17RA^−/− mice	Reduced disease severity	[43]
	Neutrophils	Source of IL-17 in effector phase	[42]
CIA	Soluble IL-17R	Suppression of arthritis	[31]
	Ad-IL-17	Exacerbation of arthritis	[31]
		Angiogenesis	[44]
	IL-17^−/− mice	Suppression of arthritis	[45]
	IL-17^−/− BM transfer	Suppression of arthritis	[46]
	a-IL-17 serum	Suppression	[47]
	a-IL-1β + a-IL-17A (sc, bs)	Suppression	[48]
	a-IL-1β or a-IL-17A (c)	Suppression	[49]
	a-IL-1β + a-IL-17A (bs, n)	Suppression	[50]
	a-IL-17 a-GM-CSF (c)	Suppression	[51]
	CD4^+ Th17 cells	Stimulation of osteoclastogenesis	[37, 52]
	V4γ^+V4δ^+  γδ T cells	IL-17 production	[53]
	IL-6	Upregulated by IL-17	[47]
		Positive feedback loop triggered by IL-17A	[54]
		Induces Th17 differentiation	[55]
	IL-1β	Upregulated by IL-17	[52]
	RANK, RANKL	Expression induced by Th17 cells	[56]
	Ad-IL-4	IL-17 mRNA levels
		Prevention of osteoclastogenesis	[57]
	IL-12p35^−/− mice	More severe arthritis
		IL-17 mRNA levels	[58]
	Ad-IL-27	Suppressed arthritis
		IL-17 levels in joint and serum
		IL-1β, IL-6, and CCL2 expression	[59]
	Ad-IL-37	Downregulates IL-17
		Inhibits Th17 proliferation	[60]
	NK cell depletion	Exacerbation of arthritis	[61]
	cells	Suppression of arthritis ( differentiation )	[62]
	IL-10R Tg mice	Increased susceptibility of arthritis (IL-17 )
		IL-17 producing γδ T cells accumulate in joint	[63]
	IL-23p19^−/− mice	Inhibition of arthritis (Th17 differentiation )	[58]
	IL-23p19 vaccine	Suppressed arthritis	[64]
	IFN-γR^−/− mice	Exacerbated arthritis	[65]
	IFN-γR^−/− mice + a-IL-17	Inhibited arthritis	[66]
PGIA	Initiation phase	Local and systemic IL-17 production	[67]
	IL-17^−/− mice	Severity and onset similar to WT	[68]
		IL-1β IL-6 expression
	IFN-γ^−/− mice	Amelioration of arthritis	[69]
		IL-17 levels
	IFNγ/IL-17^−/− mice	Suppressed arthritis	[69]
		Reduced joint damage and cellular infiltration

sc: single-chain; bs: bispecific; n: neutralizing; c: combination therapy; Ad: adenoviral; Tg: transgenic; BM: bone marrow.